Table 6. In Silico ADMET Parameters for Proposed Moleculesa.
| absorption | |||||||
|---|---|---|---|---|---|---|---|
| Com | Ws (log mol/L) | Caco2-P (log in 10–6 cm/s) | HIA (% A) | SP (log Kp) | P-gs | P-GI i | P-GII i |
| PB | –2.55 | 1.30 | 96.15 | –2.81 | no | no | no |
| BB | –3.20 | 1.62 | 100 | –2.67 | no | no | yes |
| SP | –3.09 | 1.89 | 92.85 | –2.28 | no | no | no |
| CX | –3.20 | 1.26 | 78.86 | –2.73 | no | no | no |
| MDC | –3.71 | 0.37 | 90.84 | –2.74 | yes | no | no |
| ADC | –3.60 | 0.33 | 96.29 | –2.73 | yes | no | no |
| distribution | ||||
|---|---|---|---|---|
| HVDss (log L/kg) | Hf (Fu) | BBB permeability (log BB) | CNS permeability (log PS) | |
| PB | 0.24 | 0.35 | –0.025 | –2.515 |
| BB | 0.81 | 0.35 | 0.633 | –1.675 |
| SP | 0.23 | 0.13 | 0.267 | –1.677 |
| CX | –0.66 | 0.33 | –0.653 | –3.043 |
| MDC | –0.44 | 0 | –0.603 | –2.533 |
| ADC | –0.49 | 0.05 | –0.552 | –2.365 |
| metabolism | |||||||
|---|---|---|---|---|---|---|---|
| PC-4 | CYP2D6 Sub | CYP3A4 Sub | CYP1A2 In | CYP2C19 In | CYP2C9 In | CYP2D6 In | CYP3A4 In |
| PB | no | yes | yes | no | no | no | no |
| BB | no | yes | yes | no | no | yes | no |
| SP | no | yes | yes | yes | no | no | no |
| CX | no | no | no | no | no | no | no |
| MDC | no | yes | yes | yes | yes | no | yes |
| ADC | no | yes | no | yes | yes | no | yes |
| excretion | ||
|---|---|---|
| total clearance (log mL/min/kg) | renal OCT2 Sub | |
| PB | 0.855 | yes |
| BB | 1.272 | yes |
| SP | –0.008 | no |
| CX | 0.643 | no |
| MDC | 0.171 | no |
| ADC | 0.039 | no |
| toxicity | ||||||||||
|---|---|---|---|---|---|---|---|---|---|---|
| AMES | HTD (log mg/kg/day) | h I inh | h II inh | OAT (LD50) mol/kg | OCT (LOAEL) (log mg/kg/D) | HT | SS | TP-T (log μg/L) | MT (log mM) | |
| PB | no | –0.54 | no | yes | 2.929 | 1.384 | yes | no | 0.386 | 0.032 |
| BB | no | –0.132 | no | no | 3.313 | 1.275 | no | no | 0.288 | –0.869 |
| SP | no | 0.219 | no | no | 1.959 | 2.156 | no | yes | 2.211 | 0.811 |
| CX | yes | 0.87 | no | no | 1.956 | 1.004 | yes | no | 0.284 | 2.66 |
| MDC | yes | 0.154 | no | no | 2.122 | 1.548 | yes | no | 0.34 | –0.061 |
| ADC | yes | 0.18 | no | no | 2.117 | 1.476 | yes | no | 0.327 | 0.603 |
a
PC, positive control; Com, compound; Ws, water solubility; Caco2-P, Caco2-permeability; HIA, human intestinal absorption; SP, skin permeability; P gs, P-glycoprotein substrate; P gIi, P-glycoprotein I inhibitor; P-gIIi, P-glycoprotein II inhibitor; HVDss, steady-state volume of distribution; Hf, fraction unbound (human); BBB, blood–brain barrier; CNS, central nervous system; CYP, cytochrome P; Sub, substrate; In, inhibitor; OCT2, organic cation transport 2; HTD, maximum tolerated dose (human); OAT, oral rat acute toxicity (LD50); OCT, oral rat chronic toxicity (LOAEL); HT, hepatotoxicity; SS, skin sensitization; TP-T, Tetrahymena pyriformis toxicity; MT, Minnow toxicity.